ID IMDH_DICDI Reviewed; 515 AA.
AC Q54QQ0;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 24-JAN-2024, entry version 118.
DE RecName: Full=Inosine-5'-monophosphate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMP dehydrogenase {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMPD {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMPDH {ECO:0000255|HAMAP-Rule:MF_03156};
DE EC=1.1.1.205 {ECO:0000255|HAMAP-Rule:MF_03156};
GN Name=impdh; Synonyms=guaB; ORFNames=DDB_G0283701;
OS Dictyostelium discoideum (Social amoeba).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [2]
RP PROTEIN SEQUENCE OF 118-132; 143-155; 247-256 AND 431-455, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RA Bienvenut W.V., Veltman D.M., Insall R.H.;
RL Submitted (JAN-2010) to UniProtKB.
RN [3]
RP INDUCTION.
RX PubMed=16469056; DOI=10.1111/j.1462-5822.2005.00633.x;
RA Farbrother P., Wagner C., Na J., Tunggal B., Morio T., Urushihara H.,
RA Tanaka Y., Schleicher M., Steinert M., Eichinger L.;
RT "Dictyostelium transcriptional host cell response upon infection with
RT Legionella.";
RL Cell. Microbiol. 8:438-456(2006).
CC -!- FUNCTION: Catalyzes the conversion of inosine 5'-phosphate (IMP) to
CC xanthosine 5'-phosphate (XMP), the first committed and rate-limiting
CC step in the de novo synthesis of guanine nucleotides, and therefore
CC plays an important role in the regulation of cell growth.
CC {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + IMP + NAD(+) = H(+) + NADH + XMP; Xref=Rhea:RHEA:11708,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57464,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58053;
CC EC=1.1.1.205; Evidence={ECO:0000255|HAMAP-Rule:MF_03156};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03156};
CC -!- ACTIVITY REGULATION: Mycophenolic acid (MPA) is a non-competitive
CC inhibitor that prevents formation of the closed enzyme conformation by
CC binding to the same site as the amobile flap. In contrast, mizoribine
CC monophosphate (MZP) is a competitive inhibitor that induces the closed
CC conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor
CC inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of
CC bacterial IMPDH. {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- PATHWAY: Purine metabolism; XMP biosynthesis via de novo pathway; XMP
CC from IMP: step 1/1. {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- INDUCTION: Down-regulated by Legionella pneumophila infection.
CC {ECO:0000269|PubMed:16469056}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC Rule:MF_03156}.
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DR EMBL; AAFI02000056; EAL65617.1; -; Genomic_DNA.
DR RefSeq; XP_638973.1; XM_633881.1.
DR AlphaFoldDB; Q54QQ0; -.
DR SMR; Q54QQ0; -.
DR STRING; 44689.Q54QQ0; -.
DR PaxDb; 44689-DDB0230098; -.
DR EnsemblProtists; EAL65617; EAL65617; DDB_G0283701.
DR GeneID; 8624219; -.
DR KEGG; ddi:DDB_G0283701; -.
DR dictyBase; DDB_G0283701; guaB.
DR eggNOG; KOG2550; Eukaryota.
DR HOGENOM; CLU_022552_2_1_1; -.
DR InParanoid; Q54QQ0; -.
DR OMA; MGYCGAK; -.
DR PhylomeDB; Q54QQ0; -.
DR Reactome; R-DDI-6798695; Neutrophil degranulation.
DR Reactome; R-DDI-73817; Purine ribonucleoside monophosphate biosynthesis.
DR Reactome; R-DDI-9748787; Azathioprine ADME.
DR UniPathway; UPA00601; UER00295.
DR PRO; PR:Q54QQ0; -.
DR Proteomes; UP000002195; Chromosome 4.
DR GO; GO:0005737; C:cytoplasm; ISS:dictyBase.
DR GO; GO:0045335; C:phagocytic vesicle; HDA:dictyBase.
DR GO; GO:0003682; F:chromatin binding; ISS:dictyBase.
DR GO; GO:0003938; F:IMP dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006177; P:GMP biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006183; P:GTP biosynthetic process; IBA:GO_Central.
DR CDD; cd04601; CBS_pair_IMPDH; 1.
DR CDD; cd00381; IMPDH; 1.
DR Gene3D; 3.20.20.70; Aldolase class I; 1.
DR HAMAP; MF_01964; IMPDH; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR005990; IMP_DH.
DR InterPro; IPR015875; IMP_DH/GMP_Rdtase_CS.
DR InterPro; IPR001093; IMP_DH_GMPRt.
DR NCBIfam; TIGR01302; IMP_dehydrog; 1.
DR PANTHER; PTHR11911:SF111; INOSINE-5'-MONOPHOSPHATE DEHYDROGENASE; 1.
DR PANTHER; PTHR11911; INOSINE-5-MONOPHOSPHATE DEHYDROGENASE RELATED; 1.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00478; IMPDH; 1.
DR PIRSF; PIRSF000130; IMPDH; 1.
DR SMART; SM00116; CBS; 2.
DR SMART; SM01240; IMPDH; 1.
DR SUPFAM; SSF54631; CBS-domain pair; 1.
DR SUPFAM; SSF51412; Inosine monophosphate dehydrogenase (IMPDH); 1.
DR PROSITE; PS51371; CBS; 2.
DR PROSITE; PS00487; IMP_DH_GMP_RED; 1.
PE 1: Evidence at protein level;
KW CBS domain; Cytoplasm; Direct protein sequencing; GMP biosynthesis;
KW Metal-binding; NAD; Oxidoreductase; Potassium; Purine biosynthesis;
KW Reference proteome; Repeat.
FT CHAIN 1..515
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000328152"
FT DOMAIN 120..179
FT /note="CBS 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT DOMAIN 183..239
FT /note="CBS 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 334
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 430
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 277..279
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 327..329
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 329
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 331
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 332
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 334
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 367..369
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 390..391
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 414..418
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 442
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 501
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 502
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
SQ SEQUENCE 515 AA; 56311 MW; 054EFBD2EB940868 CRC64;
MEKINKILQG TNSEYKSEWF VDGFDCFELF QQRHGYTYDD LIMLPGHINF SADDVSLKTK
LTKNISLNAP LVSSPMDTVT EHLMAINMAL LGGIGIIHYN NTVEEQVVEV KKVKRFKNGF
ITDPIVLSPT HKLSDVDMIK QKYGFSGIPI TDTGRIGGKL VGIVTSRDTD FIKDRSTTLS
EVMTTDLITG QQNCTLEEAN SILKSCKKGK LPIVNDKGEL VALASRDDLV KNRDFPMATK
DHENKKLLVG AALGTRETDK ERLAALSDAG VDVVILDSSQ GDSTYQREMI RFIKRNYPKI
DVIGGNVVTT SQCESLIQAG VDGLRVGMGV GSICTTQEVM ACGRPQATAV FKCALYSSQY
NVPIIADGGI RTIGHIIKGL SLGASSVMMG SMLAGTEEAP GDYFYKDGMR LKKYRGMGSL
EAMVKGGDQR YFSETDKIKV AQGVSGSVVD KGSVKKFVPY LIQGIKHGLQ DLGCNSVTNL
RESVYGGKVR FEVRTAAAQV EGSVHSLFSY EKHFI
//
